Molecular Characterization by High- Resolution Isoelectric Focusing of the Products Encoded by the Class II Region Lo of the Major Histocompatibility Complex in Humans. I. DR and DQ Gone Variants S. Rodriguez de Cordoba, A. Nunez-Roldan, R. Winchester, P. Marshal|, C. Carrier, N. Mo|len, M. Walker, F. Ginsberg-FeUner, and P. Rubinstein ABSTRACT: We describe a new approach to the analysis of the structural polymorphism of the DRfl DOa, and DO.J3 polypeptide chains of human histocompatibility class H antigens. In comparison to conventional two-dimensional gel studies, this method provides sharper definition of the p bands and side-by-side comparisons within the same gel, thereby permitting the a~tection of m differences in the isodectric poi~ts of the protein chains. Using this mctheddogy we have ana the IEF polymorphism and the variability in the number of the DR[3 chains encoded by differe DR haplotypes. Twenty DR[J chain variants, which include the products of no less than tw separate DR[3 loci, have been thus far identified. Alleles at one of these loci are assumed to c for DR[J chains carrying the DR all~specificities DRI, DR2, DR3, DR4, DRS, DRw6, DR7, and DRS, Allele: at a second DR[3 locus encode DR[J chains that may be shared by serologica DR-different haplotypes and carr~ supertypic serologic sI~cificities (i.e., DRw52 and DRw53 We abe demonstrate here that the structural polymo~hisms of the DQa and DQ[3 chains ar more extensive than previously thought, report the characterization of 14 DQ[3 variants, and define their relationship to the previously described DQw swologic specificities. In addition, we describe the class 11 haplotype associations observed for the different DR and DO. variants characterized. A B B R E V I A T I O N S MHC major histocompatibility corn- LCL Epstein-Bare virus transformed plex lyraphoblas¢oid cell lines MLC mixed lymphocyte culture IEF isoelectric focusing HTC homozygous typing cell From the Department of lmmunogenetics, The Lindsley F. Kimball Resea~h Institute of the ,5ie~ Center, 310 East 67tb Strict, New York. New York (S.R.C.; P.M.; C.C.; N.M.; M. W.; PER.), Cen de lnvestigaciones Bio/ogicas, Consejo Superior de Investigaciones CientiJicas (C$IC), Velazquez 144, 28006 Madrid, Spain (S.R.C.), Department of Rheumatic Diseases, The Hospital for Joint Diseases, Orthelmlic Institute, 301 East 17tO Strut, New York, New York (A.N.-R.; R.W.), and Department of Ped ?¢lount Sinai School of Medicine of the City University of New York, 1 Gustave L. Levy Pficce, New York (F.G.-F.). Address v:?ri~s ,-¢ques~J co: Dr. S. Redriguez de Cordoba, Department of lmmunogenetics, The L f . Kimball Research Institute ef the NY Blood Center, 310 East 67th Street, New York, NY 10 Received April 25, 1987; revised July 22, 1987. Human Immunology 20, 71--93 (1987) © Elsevier Science Publishing Co., Inc., 1987 52 Vanderbil¢ Ave., New York, NY 10017 71 0198-8859/87/$3.50